Precipitation is the formation of a solid in a solution during a chemical reaction. The solid is called the precipitate, and the liquid remaining above the solid is called the supernate. Solvent/non-solvent precipitation is a technique commonly employed to isolate a substance in solid form from a solution. In this process the substance particles are obtained by dissolving the substance in a solvent and then precipitating the substance by combining the substance solution with a non-solvent. Adding a non-solvent to a substance solution increases the saturation ratio of the solution causing precipitation of the solute. The solvent and the non-solvent must be at least partially soluble in each other. U.S. Pat. No. 3,953,383, U.S. Pat. No. 4,166,898, U.S. Pat. No. 3,900,424, U.S. Pat. No. 4,500,704, U.S. Pat. No. 4,066,630, U.S. Pat. No. 4,145,525, U.S. Pat. No. 3,706,713 and U.S. Pat. No. 4,975,525 teach to dissolve polymers in certain solvents and to precipitate the polymers by adding the polymer solutions to certain non-solvents.
CO2 is non-toxic, non-flammable, relatively inexpensive and recyclable gass. Its critical temperature and pressure (Tc=31.1 deg-C, Pc=7.38 MPa) are relatively mild. Supercritical CO2—where CO2 is in a fluid state while also being at or above its critical temperature and pressure—has several desirable features such as low viscosity and high solvent power for most organic solvents. Because most organic (carbon-containing) solvents are miscible (mix to foam a homogeneous solution) in supercritical CO2, it acts a non-solvent in solvent/non-solvent precipitation. Technologies based on a supercritical anti-solvent (SAS) process have been wildly used for engineering microparticles and nanoparticles. Based on employing CO2 as an anti-solvent for particle fabrication, the SAS methods include the follows: supercritical anti-solvent (GAS/SAS), precipitation with a compressed anti-solvent (PCA), aerosol solvent extraction system (ASES), solution-enhanced dispersion by supercritical CO2 (SEDS), and supercritical anti-solvent with enhanced mass transfer (SAS-EM). These method re well known in he art.
In a SAS process, the substance organic solution is sprayed into a precipitation chamber where a supercritical fluid (antisolvent) is present causing rapid contact between the two media. This generates a higher super-saturation ratio of the solution resulting in fast nucleation and growth.
The U.S. Pat. No. 5,725,836, U.S. Pat. No. 6,998,051, U.S. Pat. No. 5,803,966, U.S. Pat. No. 7,250,152, U.S. Pat. No. 6,063,910, U.S. Pat. No. 6,830,714 and U.S. Pat. No. 5,864,923 teach to use supercritical fluid as anti-solvent to precipitate or co-precipitate drugs and/or polymers.